title: Effect of MK-467 on organ blood flow parameters detected by contrast-enhanced ultrasound in dogs treated with dexmedetomidine.
abstract: OBJECTIVE
  To evaluate the dexmedetomidine-induced reduction in organ blood flow with quantitative contrast-enhanced ultrasound (CEUS) method and to observe the influence of MK-467 on such reduction.
  
  
  METHODS
  Randomized cross-over study.
  
  
  METHODS
  Six adult purpose-bred laboratory beagle dogs (mean body weight 15.3 ± 1.9 kg).
  
  
  METHODS
  Contrast-enhanced ultrasound was performed on six conscious healthy laboratory beagles. The animals on separate occasions underwent three treatments: awake without any medication (CTRL), dexmedetomidine 10 μg kg(-1) (DEX) and DEX + MK-467 500 μg kg(-1) (DMK) intravenously (IV). The kidney (10-15 minutes post-treatment), spleen (25-30 minutes post-treatment), small intestine (40-45 minutes post-treatment) and liver (50-55 minutes post-treatment) were examined with CEUS. A time curve was generated and the following perfusion parameters were analysed: arrival time (AT), time to peak from injection (TTPinj), peak intensity (PI) and wash-in rate (Wi). In addition to CEUS, renal glomerular filtration rate was indirectly estimated by the rate of iohexol elimination.
  
  
  RESULTS
  AT and TTPinj were significantly higher for DEX than for CTRL in all studied organs. The same parameters were significantly higher for DEX than for DMK in the kidney, spleen and small intestine. PI was significantly lower for DEX than for CTRL or DMK in the kidney. Wi was significantly lower for DEX than for CTRL or DMK in the kidney and significantly lower than for CTRL only in the small intestine. Plasma concentration of iohexol was significantly higher after DEX than CTRL administration.
  
  
  CONCLUSIONS
  Contrast-enhanced ultrasound was effective in detecting DEX-induced changes in blood flow. MK-467 attenuated these changes.
  
  
  CONCLUSIONS
  Clinicians should consider the effects of the sedation protocol when performing CEUS. Addition of MK-467 might beneficially impact the haemodynamic function of sedation with alpha-2 adrenoceptor agonists.
authors.affiliation: Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland.
authors.forename: Flavia
authors.initials: F
authors.lastname: Restitutti
authors.forename: Merja R
authors.initials: MR
authors.lastname: Laitinen
authors.forename: Marja R
authors.initials: MR
authors.lastname: Raekallio
authors.forename: Mari
authors.initials: M
authors.lastname: Vainionpää
authors.forename: Robert T
authors.initials: RT
authors.lastname: O'Brien
authors.forename: Erja
authors.initials: E
authors.lastname: Kuusela
authors.forename: Outi M
authors.initials: OM
authors.lastname: Vainio
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists / Q000494:pharmacology*; D000769:Anesthesia, Inhalation / Q000379:methods / Q000662:veterinary; D000818:Animals; D003287:Contrast Media; D020927:Dexmedetomidine / Q000494:pharmacology*; D004285:Dogs; D005260:Female; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D007421:Intestine, Small / Q000098:blood supply; D007472:Iohexol; D007668:Kidney / Q000098:blood supply; D008099:Liver / Q000098:blood supply; D008297:Male; D011807:Quinolizines / Q000494:pharmacology*; D012039:Regional Blood Flow / Q000187:drug effects*; D013154:Spleen / Q000098:blood supply; D014463:Ultrasonography / Q000379:methods / Q000662:veterinary
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D003287:Contrast Media; D006993:Hypnotics and Sedatives; D011807:Quinolizines; C055732:vatinoxan; D007472:Iohexol; D020927:Dexmedetomidine
keywords: MK‐467; adrenergic antagonist; alpha‐2; alpha‐2 adrenergic agonist; canine; dexmedetomidine; sedation